The goal of this project is to test the usefulness of cytotoxic monoclonal anti-Ia antibodies and anti-Ia allosera in prevention of rodent pancreatic islet allograft and senograft rejection. Pancreatic islet transplantation remains and appealing alternative to the treatment of human diabetics. The most serious impediment to islet transplantation in man is islet graft rejection. Since islet Beta cells lack the Ia antigen present on donor lymphocytes, it is postulated that incubation of islet preparations or islet cell preparations with cytotoxic allo- or monoclonal anti-Ia antibodies may selectively deplete donor islet preparations of passenger leukocytes, macrophages and other Ia bearing cells, thereby allowing long-term survival of islet allografts, and possibly islet xenografts as well. Isolated murine islets will be transplanted intransplenically into congenic, allogeneic and control isograft streptozotocin diabetic mice, and into xenogeneic rats, after donor islet or islet cell treatment with these allosera or antibody preparations. Graft function will be documented by blood glucose, serum insulin, diabetes recrurence after splenectomy, and anti-insulin, peroxidase immunohistochemistry of transplant specimens. If successful, these experiments will provide support for similar studies of donor islet treatment in eventual human islet transplantation.